Related Experiment Video
Updated: Jun 30, 2025
Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1
Published on: February 28, 2025
VapC12 ribonuclease toxin modulates host immune response during Mycobacterium tuberculosis infection
Shaifali Tyagi1,2, Srikanth Sadhu3, Taruna Sharma1,2
1Mycobacterial Pathogenesis Laboratory, Translational Health Science and Technology Institute, Faridabad, Haryana, India.
Abstract:
Mechanistic understanding of antibiotic persistence is a prerequisite in controlling the emergence of MDR cases in Tuberculosis (TB). We have reported that the cholesterol-induced activation of VapC12 ribonuclease is critical for disease persistence in TB. In this study, we observed that relative to the wild type, mice infected with ΔvapC12 induced a pro-inflammatory response, had a higher pathogen load, and responded better to the anti-TB treatment. In a high-dose infection model, all the mice infected with ΔvapC12 succumbed early to the disease. Finally, we reported that the above phenotype of ΔvapC12 was dependent on the presence of the TLR4 receptor. Overall, the data suggests that failure of a timely resolution of the early inflammation by the ΔvapC12 infected mice led to hyperinflammation, altered T-cell response and high bacterial load. In conclusion, our findings suggest the role of the VapC12 toxin in modulating the innate immune response of the host in ways that favor the long-term survival of the pathogen inside the host.
Insights
The VapC12 toxin in tuberculosis (TB) persistence is linked to host immune response. Disrupting VapC12 improves anti-TB treatment by modulating inflammation and bacterial load.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Antibiotic persistence is key to controlling multidrug-resistant (MDR) tuberculosis (TB).
- The VapC12 ribonuclease, activated by cholesterol, is crucial for TB persistence.
- Understanding VapC12's role in host-pathogen interaction is vital for new TB therapies.
Purpose of the Study:
- To investigate the role of VapC12 in the host immune response during TB infection.
- To determine the impact of VapC12 deletion on disease progression and treatment efficacy.
- To elucidate the molecular mechanisms underlying VapC12-mediated immune modulation.
Main Methods:
- Comparative analysis of wild-type and ΔvapC12 infected mouse models.
- Assessment of pro-inflammatory responses, pathogen load, and treatment outcomes.
- Investigation of the dependency on Toll-like receptor 4 (TLR4) for observed phenotypes.
Main Results:
- Mice infected with ΔvapC12 exhibited a heightened pro-inflammatory response and increased pathogen burden compared to wild-type.
- Deletion of VapC12 led to improved response to anti-TB treatment.
- The observed phenotype of ΔvapC12 was dependent on the TLR4 receptor.
- Failure to resolve early inflammation in ΔvapC12 infected mice resulted in hyperinflammation and altered T-cell responses.
Conclusions:
- VapC12 toxin plays a significant role in modulating the host's innate immune response.
- VapC12 contributes to long-term Mycobacterium tuberculosis survival by manipulating host immunity.
- Targeting VapC12 may represent a novel therapeutic strategy for combating TB, particularly MDR-TB.
Related Concept Videos
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:23Types of RNA
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...